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1.  Caloric Intake, Aging, and Mild Cognitive Impairment: A Population-Based Study 
In a population-based case-control study, we examined whether moderate and high caloric intakes are differentially associated with the odds of having mild cognitive impairment (MCI). The sample was derived from the Mayo Clinic Study of Aging in Olmsted County, Minnesota. Non-demented study participants aged 70–92 years (1,072 cognitively normal persons and 161 subjects with MCI) reported their caloric consumption within 1 year of the date of interview by completing a Food Frequency Questionnaire. An expert consensus panel classified each subject as either cognitively normal or having MCI based on published criteria. We conducted multivariable logistic regression analyses to compute odds ratios (OR) and 95% confidence intervals (95% CI) after adjusting for age, sex, education, depression, medical comorbidity, and body mass index. We also conducted stratified analyses by apolipoprotein E ε4 genotype status. Analyses were conducted in tertiles of caloric intake: 600 to <1,526 kcals per day (reference group); 1,526 to 2,143 kcals per day (moderate caloric intake group); and >2,143 kcals per day (high caloric intake group). In the primary analysis, there was no significant difference between the moderate caloric intake group and the reference group (OR 0.87, 95% CI 0.53–1.42, p = 0.57). However, high caloric intake was associated with a nearly two-fold increased odds of having MCI (OR 1.96, 95% CI 1.26–3.06, p = 0.003) as compared to the reference group. Therefore, high caloric intake was associated with MCI but not moderate caloric intake. This association is not necessarily a cause-effect relationship.
PMCID: PMC3578975  PMID: 23234878
aging; APOE ε4 genotype; caloric intake; mild cognitive impairment; population-based
2.  Association of Prior Stroke with Cognitive Function and Cognitive Impairment: A Population-based Study 
Archives of neurology  2009;66(5):614-619.
Defining the nature of the contribution of stroke to cognitive impairment remains challenging.
We randomly selected Olmsted County, MN residents aged 70–89 years on October 1, 2004 and invited eligible non-demented subjects to participate. Participants (n = 2,050) were evaluated with an informant interview, a neurological evaluation, and neuropsychological testing. Neuropsychological testing included 9 tests to assess memory, attention and executive function, visuospatial cognition and language. Subjects were diagnosed by consensus as cognitively normal, MCI (either amnestic (a-) or non-amnestic (na-)), or dementia. A history of stroke was obtained from the subject and confirmed in the medical record. We computed the odds ratios (OR) for a clinical diagnosis of MCI or for scoring in the lowest quartile on each cognitive domain.
There were 1640 cognitively normal and 329 MCI subjects, 241 a-MCI and 88 na-MCI. In fully adjusted models with non-demented subjects only, a history of stroke was associated with a higher odds ratio (OR) of na-MCI (OR= 2.85, 95% CI 1.61 – 5.04) than a-MCI (OR= 1.77, 95% CI 1.14 – 2.74). A history of stroke was also associated with impaired function in each cognitive domain except memory. The association was strongest for attention and executive function (OR=2.48, 95% CI 1.73 – 3.53). APOE e4 genotype was associated only with a-MCI and with impaired memory function.
In this population-based sample of non-demented persons, a history of stroke was particularly associated with na-MCI and with impairment in non-memory cognition. APOE e4 genotype was associated with memory impairment and a-MCI.
PMCID: PMC3050015  PMID: 19433661
3.  Physical Exercise and Mild Cognitive Impairment: A Population-Based Study 
Archives of neurology  2010;67(1):80-86.
Physical exercise was found to be associated with a decreased risk of dementia and Alzheimer disease. We investigated whether physical exercise is also associated with mild cognitive impairment (MCI).
Population-based case-control study.
The Mayo Clinic Study of Aging, an ongoing population-based cohort study in Olmsted County, Minnesota, USA.
1324 non-demented subjects who completed a questionnaire on physical exercise.
Main Outcome Measures
An expert consensus panel classified each subject as either cognitively normal or affected by MCI using information from a Clinical Dementia Rating Scale administered to the subject and to an informant, a neurological evaluation, and neuropsychological testing to assess 4 cognitive domains.
We compared the frequency of physical exercise in 198 subjects with MCI to the frequency in 1126 cognitively normal subjects and adjusted analyses for age, sex, years of education, medical comorbidity, and depression. The odds ratio (OR) for any frequency of moderate-intensity exercise was 0.61 (95% confidence interval [CI], 0.43–0.88; P=.008) for exercise in midlife (aged 50–65 years), and 0.68 (95% CI, 0.49–0.93; P=.02) for exercise in late life. The findings were consistent in men and women. Light exercise and vigorous exercise were not significantly associated with MCI.
In this population-based case-control study, any frequency of moderate-intensity exercise carried out in either midlife or late life was associated with a reduced OR of MCI.
PMCID: PMC2919839  PMID: 20065133
4.  A Prospective Study of Chronic Obstructive Pulmonary Disease and Risk of Mild Cognitive Impairment 
JAMA neurology  2014;71(5):581-588.
Previous studies suggest cross-sectional associations between a diagnosis of chronic obstructive pulmonary disease (COPD) and mild cognitive impairment (MCI). However, few studies have assessed whether COPD, a potentially modifiable factor, is associated with an increased risk of MCI and if the relation is specific to type of MCI.
To investigate whether a diagnosis of COPD, and COPD duration, is associated with an increased risk of incident MCI, and MCI subtypes (amnestic MCI (a-MCI) and non-amnestic MCI (na-MCI)).
Mayo Clinic Study on Aging, a prospective population-based cohort study.
Olmsted County, Minnesota.
The study included 1425 cognitively normal individuals aged 70–89 years, who were randomly selected from Olmsted County, MN, on October 1, 2004, using the medical records linkage system.
At baseline and every 15 months thereafter, participants were assessed with a nurse interview, neurological examination, and neuropsychological testing. A diagnosis of COPD was confirmed via medical record chart review. A baseline diagnosis of COPD and disease duration were examined as risk factors for MCI and MCI-subtypes using Cox proportional hazards models and adjusting for demographic variables and medical comorbidities, using age as the time scale.
Incident MCI, amnestic MCI, non-amnestic MCI
Of 1425 cognitively normal subjects at baseline, 370 developed incident MCI. The median duration of follow-up was 5.1 years (Interquartile Range [IQR], 3.8–5.4 years). COPD significantly increased the risk of na-MCI by 83% (HR 1.83; 95% CI, 1.04–3.23), but not any MCI or a-MCI in multivariate analyses. There was a dose-response relationship such that individuals with COPD duration of 5 years or longer at baseline had the greatest risk of both MCI (HR 1.58, 95% CI:1.04, 2.40) and na-MCI (HR 2.58, 95% CI:1.32–5.06).
COPD was associated with an increased risk of MCI, particularly na-MCI. There was a dose-response relationship between COPD duration and risk of MCI. These findings highlight the importance of COPD as a risk factor for MCI and may provide a substrate for early intervention to prevent or delay the onset and progression of MCI, particularly na-MCI.
PMCID: PMC4020948  PMID: 24637951
5.  Cardiac Disease Increases Risk of Non-amnestic Mild Cognitive Impairment: Stronger impact in women 
JAMA neurology  2013;70(3):374-382.
Non-amnestic mild cognitive impairment (naMCI), a putative precursor of vascular and other non-Alzheimer’s disease dementias, is hypothesized to have a vascular etiology. We investigated the association of cardiac disease with amnestic (aMCI) and non-amnestic (naMCI) MCI.
A prospective, population-based, cohort study with a median 4.0 years of follow-up.
Olmsted County, Minnesota.
Participants were evaluated at baseline and every 15 months using the Clinical Dementia Rating scale, a neurological evaluation, and neuropsychological testing. A diagnosis of normal cognition, MCI, or dementia was made by consensus. Cardiac disease at baseline was assessed from the participant’s medical records.
Main outcome measures
Incident MCI, aMCI, naMCI.
Among 1,450 subjects free of MCI or dementia at baseline, 366 developed MCI. Cardiac disease was associated with an increased risk of naMCI (hazard ratio [HR] 95% confidence interval; 1.77 [1.16–2.72]). However, the association varied by sex (P for interaction = .02). Cardiac disease was associated with an increased risk of naMCI (HR, 3.07 [1.58–5.99]) in women, but not in men (HR, 1.16 [0.68–1.99]. Cardiac disease was not associated with any MCI or aMCI.
Cardiac disease is an independent risk factor for naMCI, within sex comparisons showed a stronger association in women. Prevention and management of cardiac disease and vascular risk factors may reduce the risk of naMCI.
PMCID: PMC3734560  PMID: 23358884
6.  Metabolic Syndrome, Inflammation, and Non-Amnestic Mild Cognitive Impairment in Older Persons: A Population-Based Study 
The metabolic syndrome (MetS) is more strongly associated with cognitive impairment in the presence of inflammation. This suggests that the association of MetS with mild cognitive impairment (MCI) may vary with the etiology and the subtype of MCI. This study investigated the association between MetS with or without inflammation and MCI (amnestic [a-MCI] and non-amnestic [na-MCI]). We studied a randomly selected sample of 1969 subjects (ages 70 to 89 years) from Olmsted County, MN, using the Clinical Dementia Rating Scale, a neurological evaluation, and neuropsychological testing. Data for participants were reviewed for a diagnosis of normal cognition, MCI, or dementia. Clinical components of MetS were ascertained by interview and confirmed from the medical records; biochemical measurements were assayed from a blood draw. We compared 88 na-MCI cases and 241 a-MCI cases with 1640 cognitively normal subjects. MetS was not associated with either na-MCI or a-MCI. High C-reactive protein (CRP highest tertile vs lowest tertile) was associated with na-MCI (odds ratio [OR] = 1.85; 95% confidence interval [CI] = 1.05, 3.24) but not with a-MCI, after adjusting for sex, age, and years of education. The combination of MetS and high CRP (compared to no Mets and lowest CRP tertile) was associated with na-MCI (OR = 2.31; 95% CI = 1.07, 5.00), but not with a-MCI (OR = 0.96; 95% CI = 0.59, 1.54). The combined presence of MetS and high levels of inflammation is associated with na-MCI in this elderly cohort, and suggests etiologic differences in MCI subtypes.
PMCID: PMC2837096  PMID: 19568151
metabolic syndrome; insulin resistance; mild cognitive impairment; C-reactive protein; inflammation; cross-sectional study
7.  Engagement in Social Activities and Progression from Mild to Severe Cognitive Impairment: The MYHAT Study 
It is of considerable public health importance to prevent or delay the progression of mild cognitive impairment (MCI) to more severely impaired cognitive states. This study examines the risk of progression from mild to severe cognitive impairment in relation to engagement in social activities while mildly impaired and the concurrence of subsequent change in engagement with MCI progression.
Participants were 816 older adults with cognitively defined MCI (mean age 78.0 [SD = 7.4] years) from the Monongahela-Youghiogheny Healthy Aging Team (MYHAT) Study - a prospective cohort study of MCI in the community. Over three years of follow-up, 78 individuals progressed from MCI severe cognitive impairment while 738 did not progress. Risk of progression was estimated using discrete time survival analyses. The main predictors were standardized composite measures of the variety of and frequency of engagement in social activities.
Lower risk of progression from mild to severe cognitive impairment was associated with both a greater level of frequency of engagement in social activities while mildly impaired (OR = 0.72, 95% CI: 0.55–0.93, p = 0.01), and also with a slower rate of decline in the variety of activities over time (OR = 0.01, 95% CI: <0.001–0.38, p = 0.02).
Greater engagement in social activities may potentially be beneficial for preventing or delaying further cognitive decline among older adults with MCI. Alternatively, lesser engagement in social activities may be a marker of impending cognitive decline in MCI.
PMCID: PMC3578022  PMID: 23257280
MCI; leisure activities; social engagement; cognitive decline
8.  The Prevalence of Neuropsychiatric Symptoms in Mild Cognitive Impairment and Normal Cognitive Aging: A Population-Based Study 
Archives of general psychiatry  2008;65(10):1193-1198.
Little is known about the population-based prevalence of neuropsychiatric symptoms in mild cognitive impairment (MCI).
To estimate the prevalence of neuropsychiatric symptoms in MCI and normal cognitive aging in a defined population.
Cross-sectional study derived from an ongoing population-based prospective cohort study.
The Mayo Clinic Study of Aging.
We studied a random sample of 1969 non-demented participants out of the target population of 9965 elderly persons residing in Olmsted County on the prevalence date (October 1, 2004). Neuropsychiatric data were available on 319 of the 329 MCI subjects (97.0%) and on 1590 of the 1640 cognitively normal subjects (97.0%).
Neurological, cognitive, and neuropsychiatric data were gathered from the study participants. A classification of normal cognitive aging, MCI, and dementia was adjudicated by an expert consensus panel. Accordingly, 329 subjects were classified as having MCI and the remaining 1640 subjects were classified as cognitively normal.
Main Outcome Measure
The Neuropsychiatric Inventory Questionnaire (NPI-Q).
Multi-variable logistic regression analyses were conducted, after adjusting for age, sex, and education. By taking into consideration both the odds ratio and the frequency of a symptom, the most distinguishing features between the 2 groups were apathy (odds ratio [OR], 4.53; 95% confidence interval [95% CI], 3.11–6.60; P<.001), agitation (OR, 3.60; 95% CI, 2.18–5.92; P<.001), anxiety (OR, 3.00; 95% CI, 2.01–4.48; P<.001), irritability (OR, 2.99; 95% CI, 2.11–4.22; P<.001), and depression (OR, 2.78; 95% CI, 2.06–3.76; P<.001). Delusion had the highest OR (8.12; 95% CI, 2.92–22.60; P<.001); however, it was rare in both cognitively normal subjects (6/1590=0.4%) and MCI (11/319=3.4%). Thus, the population attributable risk for delusion was only 2.62% as compared to 14.60% for apathy.
Non-psychotic symptoms affected approximately 50% of subjects with MCI and 25% of cognitively normal subjects. By contrast, psychotic symptoms were rare.
PMCID: PMC2575648  PMID: 18838636
9.  Computer Activities, Physical Exercise, Aging, and Mild Cognitive Impairment: A Population-Based Study 
Mayo Clinic Proceedings  2012;87(5):437-442.
To examine the association between computer use, physical exercise, aging, and mild cognitive impairment (MCI).
Patients and Methods
The Mayo Clinic Study of Aging is a population-based study of aging and MCI in Olmsted County, Minnesota. The study sample consists of a random sample of 926 nondemented individuals aged 70 to 93 years who completed self-reported questionnaires on physical exercise, computer use, and caloric intake within 1 year of the date of interview. The study was conducted from April 1, 2006, through November 30, 2008. An expert consensus panel classified each study participant as cognitively normal or having MCI on the basis of published criteria.
Using a multivariable logistic regression model, we examined the impact of the presence during the study period of 2 lifestyle factors (physical exercise and computer use) after adjusting for a third lifestyle factor (caloric intake) on aging and MCI. We also adjusted for age, sex, education, medical comorbidity, and depression. The median daily caloric intake was significantly higher in participants with MCI than in controls (odds ratio, 1.04; 95% confidence interval, 1.02-1.06; P=.001). Participants who engaged in both moderate physical exercise and computer use had significantly decreased odds of having MCI (odds ratio [95% confidence interval], 0.36 [0.20-0.68]) compared with the reference group. In the interaction analyses, there was an additive interaction (P=.012) but not multiplicative interaction (P=.780).
In this population-based sample, the presence of both physical exercise and computer use as assessed via survey was associated with decreased odds of having MCI, after adjustment for caloric intake and traditional confounders.
PMCID: PMC3538471  PMID: 22560523
CDR, Clinical Dementia Rating; CI, confidence interval; MCI, mild cognitive impairment; OR, odds ratio
10.  Cognitive Activities and Instrumental Activity of Daily Living in Older Adults with Mild Cognitive Impairment 
This study aimed to identify differences in the implementation of cognitive activities and instrumental activities of daily living (IADLs) between healthy individuals and subjects with mild cognitive impairment (MCI).
The study included 2,498 cognitively healthy subjects (mean age, 71.2 ± 5.1 years) and 809 MCI subjects (mean age, 71.8 ± 5.4 years). The subjects were interviewed regarding their participation in cognitive activities and the implementation of IADLs.
We found a significant association between participation in any cognitive activities (p < 0.001), using a bus or a train (p < 0.001), and MCI. After adjusting for covariates, cognitive activity of any type remained significantly associated with MCI (p < 0.005) but not with the implementation of IADLs.
Our study revealed that greater participation in cognitive activity was associated with lower odds of MCI. Participation in cognitive activities may reflect differences between healthy and MCI subjects. To clarify the causal relationship between cognitive activities and MCI, further studies are required.
PMCID: PMC3843918  PMID: 24348501
Cognitive impairment; Dementia; Alzheimer's disease; Cognitive reserve

11.  Subtle Deficits in Instrumental Activities of Daily Living in Subtypes of Mild Cognitive Impairment 
Greater cognitive and functional deficits in mild cognitive impairment (MCI) are associated with higher rates of dementia. We explored the relationship between these factors by comparing instrumental activities of daily living (IADLs) among cognitive subtypes of MCI and examining associations between IADL and neuropsychological indices.
We analyzed data from 1,108 MCI and 3,036 normal control subjects included in the National Alzheimer's Coordinating Center Uniform Data Set who were assessed with the Functional Activities Questionnaire (FAQ).
IADL deficits were greater in amnestic than nonamnestic MCI, but within these subgroups, did not differ between those with single or multiple domains of cognitive impairment. FAQ indices correlated significantly with memory and processing speed/executive function.
IADL deficits are present in both amnestic MCI and nonamnestic MCI but are not related to the number of impaired cognitive domains. These cross-sectional findings support previous longitudinal reports suggesting that cognitive and functional impairments in MCI may be independently associated with dementia risk.
PMCID: PMC2948658  PMID: 20798539
Mild cognitive impairment; Functional impairment; Activities of daily living; Memory performance; Executive function
12.  Illness Representations in Older Adults with Mild Cognitive Impairment 
Little is known about patients’ understanding of a diagnosis of Mild Cognitive Impairment (MCI). The purpose of this cross-sectional descriptive study was to describe beliefs about MCI in persons diagnosed with MCI and examine correlates (demographic and health) of those beliefs. Thirty persons diagnosed with MCI completed the Illness Perception Questionnaire-MCI (IPQ-MCI), measuring eight domains of beliefs about MCI, and one scale of emotional distress. Five of them also participated in a 15-minute cognitive interview to explore responses to the IPQ-MCI. Participants correctly identified symptoms related to MCI; generally attributed MCI to aging, heredity, and abnormal brain changes; and believed MCI to be chronic, predictable, and controllable, causing little emotional distress. However, there were no consistent beliefs regarding the negative consequences of MCI or whether MCI was understandable. There were few significant correlates of beliefs. Persons with MCI are able to report their beliefs about their illness suggesting that misconceptions and gaps in knowledge can be identified and addressed with nursing interventions.
PMCID: PMC3725767  PMID: 22716654
Mild Cognitive Impairment; illness representation; cognitive disorder
13.  Clinical differences among mild cognitive impairment subtypes in Parkinson’s disease 
Mild cognitive impairment is increasingly recognized as a construct in Parkinson’s disease (PD) and occurs in about 25% of non-demented PD patients. Although executive dysfunction is the most frequent type of cognitive deficit in PD, the cognitive phenotype of PD mild cognitive impairment (PD-MCI) is broad. PD-MCI subtypes are represented by amnestic and nonamnestic domain impairment as well as single- and multiple-domain impairment. However, it is unclear whether patients with different PD-MCI subtypes also differ in other clinical characteristics besides cognitive profile.
We studied 128 PD-MCI subjects at our Movement Disorders center, comparing clinical, motor, and behavioral characteristics across the PD-MCI subtypes.
We found varying proportions of impairment subtypes: nonamnestic single-domain (47.7%), amnestic multiple-domain (24.2%), amnestic single-domain (18.8%), and nonamnestic multiple-domain (9.5%). Attentional/executive functioning and visuospatial abilities were the most frequently impaired domains. PD-MCI subtypes differed in their motor features with nonamnestic multiple-domain PD-MCI subjects showing particularly pronounced problems with postural instability and gait. Differences among PD-MCI subtypes in age, PD duration, medication use, mood or behavioral disturbances, or vascular disease were not significant.
In addition to differing cognitive profiles, PD-MCI subtypes differ in motor phenotype and severity but not in mood, behavioral, or vascular co-morbidities. Greater postural instability and gait disturbances in the nonamnestic multiple-domain subtype emphasize shared non-dopaminergic neural substrates of gait and cognition in PD. Furthermore, increased burden of cognitive dysfunction, rather than type of cognitive deficit, may be associated with greater motor impairment in PD-MCI.
PMCID: PMC3412930  PMID: 22778009
amnestic; dementia; gait; mild cognitive impairment; nonamnestic
14.  Duration and Severity of Diabetes Are Associated with Mild Cognitive Impairment 
Archives of neurology  2008;65(8):1066-1073.
It remains unknown whether diabetes mellitus is a risk factor for mild cognitive impairment (MCI).
To investigate the association of diabetes mellitus with MCI using a population-based case-control design.
Design, Setting, and Participants
Our study was conducted in subjects aged 70 through 89 years on October 1, 2004, who were randomly selected from the Olmsted County, MN, population.
Main Outcome Measure
We administered to all participants the Clinical Dementia Rating Scale, a neurological exam, and a neuropsychological evaluation including 9 tests in 4 cognitive domains to diagnose normal cognition, MCI, or dementia. We assessed history of diabetes, diabetes treatment, and complications by interview and we measured fasting blood glucose. History of diabetes was also confirmed using a medical records-linkage system.
We compared 329 patients with MCI to 1640 subjects free of MCI and of dementia. The frequency of diabetes was similar in subjects with MCI (20.1%) and in subjects without MCI (17.7%; odds ratio [OR], 1.16; 95% confidence interval [CI], 0.85-1.57). However, MCI was associated with onset of diabetes before age 65 years (OR, 2.20; 95% CI, 1.29-3.73), diabetes duration ≥10 years (OR, 1.76; 95% CI, 1.16-2.68), treatment with insulin (OR, 2.01; 95% CI, 1.22-3.31), and presence of complications (OR, 1.80; 95% CI, 1.13-2.89) after adjustment for age, sex, and education. Analyses using alternative definitions of diabetes yielded consistent findings.
These findings suggest an association between earlier onset, longer duration, and greater severity of diabetes and MCI.
PMCID: PMC2630223  PMID: 18695056
15.  Prayer at Midlife is Associated with Reduced Risk of Cognitive Decline in Arabic Women 
Current Alzheimer research  2013;10(3):340-346.
Midlife habits may be important for the later development of Alzheimer's disease (AD). We estimated the contribution of midlife prayer to the development of cognitive decline.
In a door-to-door survey, residents aged ≥65 years were systematically evaluated in Arabic including medical history, neurological, cognitive examination, and a midlife leisure-activities questionnaire. Praying was assessed by the number of monthly praying hours at midlife. Stepwise logistic regression models were used to evaluate the effect of prayer on the odds of mild cognitive impairment (MCI) and AD versus cognitively normal individuals.
Of 935 individuals that were approached, 778 [normal controls (n=448), AD (n=92) and MCI (n=238)] were evaluated. A higher proportion of cognitively normal individuals engaged in prayer at midlife [(87%) versus MCI (71%) or AD (69%) (p<0.0001)]. Since 94% of males engaged in prayer, the effect on cognitive decline could not be assessed in men. Among women, stepwise logistic regression adjusted for age and education, showed that prayer was significantly associated with reduced risk of MCI (p=0.027, OR=0.55, 95% CI 0.33-0.94), but not AD. Among individuals endorsing prayer activity, the amount of prayer was not associated with MCI or AD in either gender.
Praying at midlife is associated with lower risk of mild cognitive impairment in women.
PMCID: PMC3754426  PMID: 23116476
Alzheimer's disease; Arabic; dementia; epidemiology; leisure; mild cognitive impairment; prayer
16.  Mild Cognitive Impairment in Parkinson’s Disease 
Minerva Medica  2011;102(6):441-459.
While Parkinson’s disease (PD) traditionally has been defined by its characteristic motor hallmarks, non-motor features such as cognitive impairment and dementia are increasingly recognized as part of PD. Mild cognitive impairment is common in non-demented PD patients, occurring in about 20-50%. Frequency estimates and clinical features of mild cognitive impairment in PD (PD-MCI), however, vary across studies due to methodological differences and lack of uniform diagnostic criteria for PD-MCI. Overall, PD-MCI patients exhibit nonamnestic deficits in cognitive domains such as executive function, attention, and visuospatial function; however, the cognitive phenotype of PD-MCI is heterogeneous with some patients demonstrating greater amnestic deficits. PD-MCI patients, particularly those with posterior cortical profiles, may be at high risk for developing dementia. Various biomarkers studied in PD-MCI including cerebrospinal fluid, genetic analyses, and neuroimaging suggest that there may be distinct PD-MCI profiles. Future studies using uniform PD-MCI diagnostic criteria and incorporating biomarkers and longitudinal follow-up of PD-MCI cohorts are needed to understand PD-MCI as a transitional state between normal cognition and dementia.
PMCID: PMC3370887  PMID: 22193376
Parkinson’s disease; dementia; mild cognitive impairment; executive dysfunction; cognitive domains
17.  Neuropsychiatric symptoms in MCI subtypes: the importance of executive dysfunction 
Mild cognitive impairment (MCI) is a syndrome thought to be a prodrome of dementia for some patients. One subtype, amnestic MCI, may be specifically predispose patients to develop Alzheimer’s Dementia (AD). Since dementia has been associated with a range of neuropsychiatric symptoms (NPS), we sought to examine the prevalence of NPS in MCI and its subtypes.
1779 participants in the National Alzheimer Coordinating Center (NACC) with MCI were included in this study. All participants were evaluated systematically with a thorough cognitive battery, clinical interview, and consensus diagnoses, and subtyped as: 1) amnestic (aMCI) (single- or multiple-domain) vs. non-amnestic (non-aMCI); 2) executive dysfunction-MCI (exMCI) (single- or multiple-domain) vs. no executive dysfunction-MCI (non-exMCI); 3) both aMCI and exMCI; 4) and neither aMCI nor exMCI. Additionally , aMCI vs. nonaMCI and exMCI vs. non-exMCI dichotomies were explored. NPS were assessed with the Neuropsychiatric Inventory (NPI-Q) and Geriatric Depression Scale (GDS).
1379 participants (77.5%) met criteria for aMCI and 616 (34.6%) for exMCI. No differences were observed in the prevalence of NPS between aMCI vs. non-aMCI. However, exMCI was associated with greater severity of depression, anxiety, agitation, disinhibition, irritability, and sleep problems, although these differences do not persist after adjustment for several variables. .
While there were few associations between aMCI and NPS, the presence of executive dysfunction in MCI was associated with greater severity of symptoms and specifically with depression (evidenced by GDS score) and anxiety. These findings may have implications for MCI prognosis and need to be explored in longitudinal studies.
PMCID: PMC3204866  PMID: 20845402
Mild Cognitive Impairment; Depression; Executive Dysfunction; Neuropsychiatric symptoms
18.  Cognitive impairment in non-1 demented oldest-old: Prevalence and relationship to cardiovascular risk factors 
To determine the prevalence and types of cognitive impairment in a sample of non-demented aged 90 and older (the oldest-old) and to examine the relationships between cognitive impairment and cardiovascular risk factors.
420 non-demented participants from The 90+ Study, a study of aging and dementia in the oldest-old. Participants were categorized into four non-overlapping groups: normal cognition, amnestic mild cognitive impairment (aMCI), non-amnestic MCI (naMCI), and other cognitive impairment (OCI). History of cardiovascular risk factors was assessed through self-report.
The overall prevalence of cognitive impairment in non-demented was 34.0% (95%CI: 29.5–38.5). The prevalence of OCI was highest (17.4%; 95%CI: 13.9–21.4) followed by aMCI (8.3%; 95%CI: 5.9–11.4) and naMCI (8.3%; 95%CI: 5.9–11.4). Normal cognition was present in 66.0% (95%CI: 61.2–70.5) of participants. History of hypertension and stroke were the only risk factors that varied between the groups, occurring more frequently in participants with naMCI (χ2=3.82; p<0.05) and OCI (χ2=5.51; p<0.05).
This study found a high prevalence of cognitive impairment in a sample of non-demented oldest-old. We did not find a strong relationship between cardiovascular risk factors and the cognitive impairment groups other than between hypertension and naMCI and stroke and OCI. Future studies comparing the incidence of dementia in these groups will ultimately determine their predictive utility in the oldest-old.
PMCID: PMC3276712  PMID: 22055654
mild cognitive impairment; oldest-old; cardiovascular risk factors
To compare rates of Mild Cognitive Impairment (MCI) and rates of progression to dementia, using different MCI diagnostic systems
MCI was investigated at baseline in 3063 community-dwelling non-demented elderly in the Ginkgo Evaluation of Memory (GEM) study who were evaluated every six months to identify presence of dementia. Overall MCI frequency was determined using (1) Clinical Dementia Rating (CDR) score of 0.5 and (2) neuropsychological (NP) criteria, defined by impairment on standard cognitive tests.
40.2% of participants met CDR MCI criteria and 28.2% met NP MCI criteria (amnestic-MCI=16.6%). 15.7% were classified as MCI by both criteria and 47.4% as Normal by both. Discordant diagnoses were observed in 24.5% who met NP Normal/CDR MCI; and 12.4% who met NP MCI/CDR Normal. Factors associated with CDR MCI among NP Normal included, lower education, lower NP scores, more IADL impairment, greater symptoms of depression and subjective health problems. Individuals meeting NP MCI/CDR normal were significantly more likely to develop dementia over the median follow up of 6.1 years than those meeting NP Normal/CDR MCI.
Different criteria produce different MCI rates and different conversion rates to dementia. Although a higher percentage of MCI was identified by CDR than NP, a higher percentage of NP MCI progressed to dementia. These findings suggest that the CDR is sensitive to subtle changes in cognition not identified by NP algorithm but is also sensitive to demographic and clinical factors probably leading to a greater number of false positives. These results suggest that identifying all individuals with CDR scores of 0.5 as Alzheimer's disease is not advisable.
PMCID: PMC2698042  PMID: 19279031
Clinical Dementia Rating Scale; Neuropsychological tests
20.  Coronary heart disease is associated with non-amnestic mild cognitive impairment 
Neurobiology of aging  2008;31(11):1894-1902.
The progression of amnestic mild cognitive impairment (a-MCI) to Alzheimer’s disease and hypothesized progression of non-amnestic mild cognitive impairment (na-MCI) to non-degenerative or vascular dementias suggest etiologic differences. We examined the association between coronary heart disease (CHD) and mild cognitive impairment (MCI) subtypes in a population-based cohort. Participants (n = 1969; aged 70-89 years) were evaluated using the Clinical Dementia Rating Scale, a neurological examination, and neuropsychological testing for diagnoses of normal cognition, MCI, or dementia. CHD was defined as a history of myocardial infarction, angina, angiographic coronary stenosis, or coronary revascularization and ascertained by participant interview and from medical records. CHD was significantly associated with Na-MCI (OR = 1.93; 95% CI = 1.22-3.06) but not with a-MCI (OR = 0.94; 95% CI = 0.69-1.28). In contrast, ApoE ε4 allele was significantly associated with a-MCI (OR = 1.75; 95% CI = 1.28-2.41), but not with na-MCI (OR = 1.17, 95% CI = 0.69-2.00). The association of CHD with prevalent na-MCI but not with a-MCI suggests that CHD and na-MCI may have similar underlying etiologies.
PMCID: PMC2888961  PMID: 19091445
Cognitive impairment; Coronary heart disease; Myocardial infarction; Angina; Coronary artery bypass grafting; Population-based
21.  Taking Care of Older Adults with Mild Cognitive Impairment: An Update for Nurses Journal of Gerontological Nursing (in press) 
Mild cognitive impairment (MCI) is a mild decline in single or multiple cognitive domains, while global cognition and basic activities of daily living remain intact. Nurses play an important role in early detection of MCI and providing care to maintain maximum independence for persons with MCI. This update seeks to provide nurses with a review of the most recent research regarding the etiology and diagnosis of MCI, risk and protective factors related to MCI, patients and their families' experience of MCI, and current interventions for persons with MCI. This update provides research evidence to inform nursing practice of MCI care.
PMCID: PMC3587112  PMID: 23189995
Mild Cognitive Impairment; Alzheimer's disease; Instrumental Activities of Daily Living; Cognition; Risk factors; Non-pharmacological interventions
22.  The incidence of MCI differs by subtype and is higher in men 
Neurology  2012;78(5):342-351.
Although incidence rates for mild cognitive impairment (MCI) have been reported, few studies were specifically designed to measure the incidence of MCI and its subtypes using published criteria. We estimated the incidence of amnestic MCI (aMCI) and nonamnestic MCI (naMCI) in men and women separately.
A population-based prospective cohort of Olmsted County, MN, residents ages 70–89 years on October 1, 2004, underwent baseline and 15-month interval evaluations that included the Clinical Dementia Rating scale, a neurologic evaluation, and neuropsychological testing. A panel of examiners blinded to previous diagnoses reviewed data at each serial evaluation to assess cognitive status according to published criteria.
Among 1,450 subjects who were cognitively normal at baseline, 296 developed MCI. The age- and sex-standardized incidence rate of MCI was 63.6 (per 1,000 person-years) overall, and was higher in men (72.4) than women (57.3) and for aMCI (37.7) than naMCI (14.7). The incidence rate of aMCI was higher for men (43.9) than women (33.3), and for subjects with ≤12 years of education (42.6) than higher education (32.5). The risk of naMCI was also higher for men (20.0) than women (10.9) and for subjects with ≤12 years of education (20.3) than higher education (10.2).
The incidence rates for MCI are substantial. Differences in incidence rates by clinical subtype and by sex suggest that risk factors for MCI should be investigated separately for aMCI and naMCI, and in men and women.
PMCID: PMC3280046  PMID: 22282647
23.  The Combination of Dysexecutive and Amnestic Deficits Strongly Predicts Conversion to Dementia in Young Mild Cognitive Impairment Patients: A Report from the Gothenburg-Oslo MCI Study 
The present study aimed to add to the knowledge of mild cognitive impairment (MCI) by studying the prognosis in a relatively young cohort of patients characterized by neuropsychological criteria.
Patients (mean age: 63 years) with cognitive complaints and MCI (n = 302) were recruited from two university clinics and followed for 2 years.
Pure dysexecutive MCI occurred in 11.7% of the neuropsychologically impaired patients, while 59.3 and 29.0% were characterized as having pure amnestic MCI or multidomain MCI. During the study period, the state of 2 (10.5%) of the patients with single-domain dysexecutive MCI converted to dementia, while 28 (29.2%) of the patients with pure amnestic MCI became demented. Of the patients with both executive and amnestic deficits, 28 (59.6%) became demented.
The results suggest that dysexecutive symptoms in combination with amnestic symptoms constitute a strong risk factor for dementia in young MCI patients. A significant number of patients in all subgroups showed normal test results at follow-up, indicating that a neuropsychological diagnosis needs to be supported by imaging or biomarker data.
PMCID: PMC4024495  PMID: 24847346
Dysexecutive mild cognitive impairment; Amnestic mild cognitive impairment; Multidomain mild cognitive impairment; Prognosis of mild cognitive impairment

24.  Content Validity and Acceptability of the Daily Enhancement of Meaningful Activity Program Intervention for Mild Cognitive Impairment Patient-Spouse Dyads 
Persons with mild cognitive Impairment (PwMCI) are at greater risk for developing Alzheimer’s disease and they experience various difficulties that decrease their quality of life. Very few interventions focus on helping PwMCI improve or maintain functional performance and enhance quality of life through meaningful activity engagement. The purpose of the study was to explore PwMCI and their spouses’ perspectives on the content validity, usefulness, and acceptability of the daily enhancement of meaningful activity (DEMA) program, which included 6 bi-weekly face-to-face sessions, between session assignments, and a self-management tool kit of written educational handouts. Nine PwMCI-care partner dyads participated in three focus groups (PwMCI alone, spouses alone, couples) to capture their perspectives on DEMA. The transcribed focus group data were analyzed through content analysis. The three groups provided support for content validity and acceptability of the program, and they suggested additional content areas important to couples experiencing MCI. They also attested to the usefulness of the tool kit and gave suggestions for its further improvement. The findings provide evidence of the content validity and acceptability of the DEMA program. A pilot study to assess feasibility and preliminary efficacy of the DEMA on health-related outcomes is the recommended next research step for this program.
PMCID: PMC3220889  PMID: 22089409
patient care partner; mild cognitive impairment; acceptability of program; program evaluation
25.  Amnestic Mild Cognitive Impairment and Early Alzheimer's Disease in an Asian Memory Clinic – Evidence for a Clinical Spectrum 
To determine if mild cognitive impairment (MCI) represents a continuum of cognitive and functional deficits.
Clinical data of 164 subjects with no dementia (ND, n = 52), uncertain dementia (n = 69), and mild probable Alzheimer's disease (AD, n = 43) were reviewed. Uncertain dementia patients were classified as pre-MCI (n = 11), early amnestic MCI (e-aMCI, n = 15) and late amnestic MCI (l-aMCI, n = 15). Cognitive assessments [Chinese Mini-Mental State Examination (CMMSE) and a validated neuropsychological battery], functional assessments (Lawton's scale for instrumental activities of daily living) and neuroimaging (ischemic lesions and medial temporal lobe atrophy) were reviewed.
ND, aMCI and mild AD subjects demonstrated a significant trend for worsening performance for all cognitive and functional measures (ANOVA, p < 0.05). Pre-MCI subjects performed significantly better than aMCI subjects in all verbal memory domains (p < 0.001), while l-aMCI had worse functional performance (p = 0.007), a trend towards greater depressive symptoms (p = 0.05) and higher medial temporal lobe atrophy scores (p = 0.06). l-aMCI subjects were more likely than either pre-MCI or e-aMCI to progress to dementia over a mean follow-up period of 2.5 years (46.7 vs. 9.1 and 20.0%, respectively).
Clinical delineation of aMCI allows the differentiation of those likely to progress for better correlation to biomarker development.
PMCID: PMC3199896  PMID: 22163238
Alzheimer's disease; Clinical dementia rating; Disease spectrum; Mild cognitive impairment

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